The goal of this project is to bring together an interdisciplinary team of researchers to test the hypothesis that urine metabolic and proteomic biomarkers can predict the response to therapy for human lower urinary tract symptoms (LUTS) and identify the most appropriate animal models for mechanistic studies of LUTS. Current data are most consistent with the idea that human LUTS has multiple etiologies and multiple manifestations. Plausible etiologies for LUTS include, but are not limited to, benign prostatic hyperplasia, inflammation in the prostate and bladder neck, changes in smooth muscle tone in the prostate and bladder neck, and neurologic changes in the lower urinary tract. Ideally, treatment for LUTS would take into account the different manifestations of disease to achieve more rapid and effective therapy for individual patients. Barriers to achieving this goal include the lack of adequate biomarkers to stratify the different manifestations of human LUTS and a lack of clarity regarding the most appropriate animal models for mechanistic studies of the different manifestations of LUTS. To address these barriers to progress in the field, this project will conduct experiments organized into three Specific Aims. Aim 1 will identify urine biomarkers of human LUTS using proteomic and metabolomic approaches. Aim 2 will identify changes in biomarker expression that correlate with effective treatment of LUTS symptoms. Aim 3 will conduct interspecies comparative studies to identify biomarker similarities among human LUTS patients, mice with bacterial prostatitis, and mice with hormone-induced urinary obstruction. It is anticipated that completion of these Aims will identify biomarkers that can stratify LUTS into different disease sub-types, predict response to therapy, and identify animal models that are most appropriate for investigating the underlying mechanisms associated with different sub-types of LUTS. Completion of these Aims will also create a base of knowledge needed to support a more comprehensive interdisciplinary project to determine the underlying cause(s) of LUTS using human patient data and data from animal models with different manifestations of urinary tract disease.